34 research outputs found
Long term follow-up and further molecular and histopathological studies in the LGMD1F sporadic TNPO3-mutated patient
No full textAdvancements in Large-Scale Volumetric PIV and PTV
No full textParticle Image Velocimetry (PIV) is considered nowadays the state-of-the-art for non-intrusive and quantitative 3D velocity measurements. Its ability to measure the velocity field around complex geometries is a valuable tool that engineers can exploit for aerodynamic design optimization in various domains, such as aerospace, wind turbines and automotive, among others. Despite recent advancements, performing a PIV measurement in the industrial environment remains challenging due to several reasons: achieving large-scale measurements, complex geometries and high Reynolds numbers. The introduction of helium-filled soap bubbles, new Lagrangian Particle Tracking (LPT) algorithms and Robotic Volumetric PIV has allowed for the measurement of large-scale volumes around complex geometries. However, despite the described advancements, large-scale PIV and LPT measurements for industrial aerodynamics require further development to accelerate their applications. The first bottleneck considered is the maximum measurable velocity. For aerodynamic flows in the transport sector, the velocity is often larger than 50 m/s when considering aircraft and race cars. To apply the mentioned techniques, acquisition frequencies higher than the one commonly available are needed. The double-frame timing strategy, characterized by image pairs with a small time separation, is detrimental to the measurement accuracy, especially when low aperture systems, such as Robotic Volumetric PIV, are considered. This research has led to the development of novel acquisition strategies (chapters 3 and 4) that improve the accuracy of double-frame velocity measurements suited for high speed applications (U∞ > 50 m/s). Another current topic of research concerns the detection of data outliers in PIV measurements, which affect their reliability and trustfulness. In this thesis (chapter 5) a novel approach to outliers detection from time-averaged three dimensional PIV data is introduced. The principle invokes the physical mechanism of turbulence transport and is based on the agreement of the measured data to the turbulent kinetic energy (TKE) transport equation. The application of this new criterium to several experimental databases shows that spurious data can be detected more easily and unambiguously as an outlier along with a low fraction of false positives. This research also attempts to decrease the gap between Computational Fluid Dynamics’ (CFD) and experiments’ aerodynamic data. In chapter 6, the application of PIV data for data assimilation is discussed. Data assimilation is a discipline in which observation and numerical or theoretical models are combined. This can be performed with two possible aims: improving the observation with physics-based models or increasing the capability of the model to represent reality. In this thesis, the latter is considered. A novel state observer technique is investigated for the assimilation of three-dimensional velocity measurements into computational fluid dynamics simulations based on Reynolds-averaged Navier–Stokes (RANS) equations. The state observer approach locally forces the solution to comply with the reference value, with increasing benefits when the density of forced points, or forcing density, is increased.Aerodynamic
Extending the velocity range of Robotic Volumetric PIV: Desing and application of a multi-Δt approach
No full textCar industry and motorsport development nowadays strongly rely on wind tunnel testing. As the literature survey shows, in order to fully understand the characteristics of the flow around a car, large-scale and volumetric flow field measurements are required. For its features, PIV can be pointed as a useful technique for automotive wind tunnels. However, its use in an automotive wind tunnel is strongly conditioned by the industrial environment itself, which requires particular efforts for what concerns safety and economic aspects.The advent of Robotic Volumetric PIV has permitted the measurement of time-averaged properties of large-scale complex aerodynamic flows by the combination of coaxial volumetric velocimetry and robotics. Firstly, the use of Helium Filled Soap Bubbles as seeding permits to enlarge the measurement volume due to their higher scattering capability. Furthermore, the compactness of the coaxial velocimetry probe together with the robotic actuation allows to measure large-scale volumes, partitioning the entire volume and reconstructing the time-averaged flow filed from multiple PIV acquisitions.Since its presentation, Robotic Volumetric PIV has been used to investigate low velocities flows, with free-stream values ranging between 2 m/s and 14 m/s. More specifically, 15 m/s can be considered the largest velocity that can be analysed with the state-of-the-art of the system due to its hardware limitations in the maximum acquisition frequency. For this reason, to meet the requirements in terms of flow velocities proper of industrial environments, the range of analysable velocities has to be extended. To address the identified requirement of high-speed volumetric measurements, a new acquisition technique has been designed and proposed. Even if a standard double-pulse strategy can measure high-speed flows due to the short time that can elapse between the two subsequent pulses, in order to increase the accuracy of the final results, a two- method is proposed. Firstly, a predictor is built using a Double-Pulse, Double-Frame acquisition with a short pulse separation time . Afterwards, the predictor is used to allow the stretching of the second pulse separation time without encountering errors given by the false pairing that would be present due to the longer displacement of the particles. To test the performance of the new method, the near wake of a replica of the Ahmed body with a 25 slant angle has been studied through an experimental campaign in the Open Jet Facility (OJF) of TU Delft. Firstly, a measurement at 12 m/s has been performed in order to be able to assess the performances of the proposed method w.r.t. the time-resolved acquisition strategy and the DP standard -DF approach. Afterwards, an airspeed of 20 m/s has been considered, in order to demonstrate the capability of the new technique of extending the velocity range of Robotic Volumetric PIV. The conducted measurements demonstrate the possibility of extending the velocity range of the Robotic Voluemtric PIV system with the proposed method. However, this is achieved at the expense of a lower accuracy, due to the lack of temporal information, and a longer measurement time, given by the necessity of multiple acquisitions.Aerospace Engineerin
Fibrosis and inflammation are greater in muscles of beta-sarcoglycan-null mouse than mdx mouse
No full textThe Sgcb-null mouse, with knocked-down β-sarcoglycan, develops severe muscular dystrophy as in type 2E human limb girdle muscular dystrophy. The mdx mouse, lacking dystrophin, is the most used model for Duchenne muscular dystrophy (DMD). Unlike DMD, the mdx mouse has mild clinical features and shows little fibrosis in limb muscles. To characterize ECM protein deposition and the progression of muscle fibrosis, we evaluated protein and transcript levels of collagens I, III and VI, decorin, and TGF-β1, in quadriceps and diaphragm, at 2, 4, 8, 12, 26, and 52 weeks in Sgcb-null mice, and protein levels at 12, 26, and 52 weeks in mdx mice. In Sgcb-null mice, severe morphological disruption was present from 4 weeks in both quadriceps and diaphragm, and included conspicuous deposition of extracellular matrix components. Histopathological features of Sgcb-null mouse muscles were similar to those of age-matched mdx muscles at all ages examined, but, in the Sgcb-null mouse, the extent of connective tissue deposition was generally greater than mdx. Furthermore, in the Sgcb-null mouse, the amount of all three collagen isoforms increased steadily, while, in the mdx, they remained stable. We also found that, at 12 weeks, macrophages were significantly more numerous in mildly inflamed areas of Sgcb-null quadriceps compared to mdx quadriceps (but not in highly inflamed regions), while, in the diaphragm, macrophages did not differ significantly between the two models, in either region. Osteopontin mRNA was also significantly greater at 12 weeks in laser-dissected highly inflamed areas of the Sgcb-null quadriceps compared to the mdx quadriceps. TGF-β1 was present in areas of degeneration-regeneration, but levels were highly variable and in general did not differ significantly between the two models and controls. The roles of the various subtypes of macrophages in muscle repair and fibrosis in the two models require further study. The Sgcb-null mouse, which develops early fibrosis in limb muscles, appears more promising than the mdx mouse for probing pathogenetic mechanisms of muscle fibrosis and for developing anti-fibrotic treatments. Highlights • The Sgcb-null mouse develops severe muscular dystrophy, the mdx mouse does not. • Fibrosis developed earlier in Sgcb-null quadriceps and diaphragm than mdx. • Macrophages were commoner in mildly inflamed parts of Sgcb-null quadriceps than mdx. • The Sgcb-null model appears more useful than mdx for studying fibrotic mechanisms. • The Sgcb-null model also appears more useful for developing anti-fibrotic treatments
Myopathic changes associated with psychomotor delay and seizures caused by a novel homozygous mutation in TBCK
No full textBackground: Biallelic mutations in TBC1-domain containing kinase (TBCK) lead to hypotonia, global developmental delay with severe cognitive and motor deficits, and variable presentation of dysmorphic facial features and brain malformations. It remains unclear whether hypotonia in these individuals is purely neurogenic, or also caused by progressive muscle disease. Methods: Whole exome sequencing was performed on a family diagnosed with nonspecific myopathic changes by means of histological analysis and immunohistochemistry of muscle biopsy samples. Results: A novel homozygous truncation in TBCK was found in two sisters diagnosed with muscle disease and severe psychomotor delay. TBCK was completely absent in these patients. Conclusions: Our findings identify a novel early truncating variant in TBCK associated with a severe presentation and add muscle disease to the variability of phenotypes associated with TBCK mutations. Inconsistent genotype/phenotype correlation could be ascribed to the multiple roles of TBCK in intracellular signaling and endolysosomal function in different tissues
Effect of streptozotocin-induced diabetes on the gene expression and biological activity of 3 beta-hydroxysteroid dehydrogenase in the rat spinal cord
No full textAbnormal secretion of steroids by the adrenals
and gonads is one of the disturbances occurring in diabetics
but the impact of diabetes on steroid formation in the nervous
system has never been studied. However, it is well
known that numerous actions of peripheral steroids on the
nervous system require their conversion into neuroactive
metabolites within the neural tissue. As this in situ steroid
synthesis/metabolism is crucial for the control of several
neurobiological functions, we investigated the effects of
streptozotocin-induced diabetes on the gene expression and
activity of 3 -hydroxysteroid dehydrogenase in the spinal
cord, a pivotal structure involved in sensorimotor and neurovegetative
mechanisms. 3 -Hydroxysteroid dehydrogenase
is a key enzyme which participates to the biosynthesis
of all classes of steroids by converting 5-3 -hydroxysteroids
such as pregnenolone and dehydroepiandrosterone
into 4-3-ketosteroids as progesterone and androstenedione,
respectively. Reverse transcription coupled with quantitative
real-time polymerase chain reaction revealed that 3 -hydroxysteroid
dehydrogenase gene was over-expressed in the spinal
cord of streptozotocin-treated rats compared with controls.
Pulse-chase experiments combined with high performance
liquid chromatography and continuous flow detection
of newly-synthesized steroids showed an increase of 3 -
hydroxysteroid dehydrogenase activity responsible for a hyper-
production of progesterone in the spinal cord of diabetic
rats. This up-regulation of progesterone biosynthesis was
concomitant with a decrease of its transformation into tetrahydroprogesterone,
a process which facilitated progesterone
accumulation in the spinal cord of streptozotocin-treated
rats. Since progesterone is a potent neuroprotective steroid,
increase of its production appeared as an endogenous molecular
and biochemical mechanism triggered by spinal nerve
cells to cope with degenerative effects of streptozotocininduced
diabetes. Our results constitute the first direct evidence
showing an impact of diabetes on steroid biosynthetic
and metabolic pathways in the nervous system. The data
open new perspectives for the modulation of deleterious
effects of diabetes by neuroprotective steroids
Outlier detection for PIV statistics based on turbulence transport
No full textThe occurrence of data outliers in PIV measurements remains nowadays a problematic issue; their effective detection is relevant to the reliability of PIV experiments. This study proposes a novel approach to outliers detection from time-averaged three-dimensional PIV data. The principle is based on the agreement of the measured data to the turbulent kinetic energy (TKE) transport equation. The ratio between the local advection and production terms of the TKE along the streamline determines the admissibility of the inquired datapoint. Planar and 3D PIV experimental datasets are used to demonstrate that in the presence of outliers, the turbulent transport (TT) criterion yields a large separation between correct and erroneous vectors. The comparison between the TT criterion and the state-of-the-art universal outlier detection from Westerweel and Scarano (Exp Fluids 39:1096–1100, 2005) shows that the proposed criterion yields a larger percentage of detected outliers along with a lower fraction of false positives for a wider range of possible values chosen for the threshold. Graphical abstract: [Figure not available: see fulltext.]Aerodynamic
A novel homozygous ISPD gene mutation causing phenotype variability in a consanguineous family
No full textWithin the group of muscular dystrophies, dystroglycanopathies represent an important subgroup of recessively inherited disorders. Their severity varies from the relatively mild forms of adult-onset limb-girdle muscular dystrophy (LGMD), to the severe congenital muscular dystrophies (CMD) with cerebral and ocular involvement. We describe 2 consanguineous children of Pakistani origin, carrying a new homozygous missense mutation c.367G>A (p.Gly123Arg) in the ISPD gene. Mutations in this gene have been recently reported as a common cause of congenital and limb-girdle muscular dystrophy. Patient 1 is an 8-year-old female with an intermediate phenotype between CMD and early LGMD; patient 2 is a 20-month-old male and second cousin of patient 1, showing a CMD phenotype. Cognitive development, brain MRI, eye examination, electrocardiogram and echocardiogram were normal in both patients. To our knowledge, this is the first report on the co-occurrence of both a CMD/early LGMD intermediate phenotype and a CMD within the same family carrying a homozygous ISPD mutation
Complete loss of the DNAJB6 G/F domain and novel missense mutations cause distal-onset DNAJB6 myopathy
No full textProtein aggregation is a common cause of neuropathology. The protein aggregation myopathy Limb-Girdle Muscular Dystrophy 1D (LGMD1D) is caused by mutations of amino acids Phe89 or Phe93 of DNAJB6, a co-chaperone of the HSP70 anti-aggregation protein. Another DNAJB6 mutation, Pro96Arg, was found to cause a distal-onset myopathy in one family
Steroid Hormones and Growth Factors Act in an Integrated Manner at the Levels of Hypothalamic Astrocytes
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